There is a need for a degradable material for use in embolization treatment. Embolization involves the introduction of a material into the vasculature in order to block the blood flow in a particular region. This procedure may be used to treat non-cancerous tumors, such as uterine fibroids, and cancerous tumors. Vascular occlusion in the case of tumors may be used to suppress pain, limit blood loss during surgery, or to cause tumor necrosis. In addition, embolization treatment may be used to control bleeding caused by conditions such as stomach ulcers, aneurysms, and injury.
One type of embolic material is preformed hydrogel microspheres; both nondegradable and degradable hydrogel microspheres have been described.
Non-degradable hydrogel microspheres have been produced and used in tissue augmentation and embolization treatments (see for example, U.S. Pat. No. 6,218,440, U.S. Pat. No. 4,446,261, U.S. Pat. No. 6,436,424, JP1994056676A, and copending and commonly owned and commonly owned U.S. Patent Application Publication Nos. 2007/0237956 and 2007/0237742). However, a degradable embolic material could enable the administration of a number of different therapies (e.g., drug delivery and surgery) to a site without permanently occluding the site from blood flow. This could lead to more effective therapies and better patient response to treatments.
Degradable hydrogel microspheres are also known in the art. One type of degradable microsphere incorporates degradable crosslinks. As the crosslinks degrade, the microsphere breaks down into soluble polymer chains (see for example U.S. Pat. No. 6,713,646, U.S. Pat. No. 6,884,905, and WO 2003/094930). Another type of degradable microsphere is prepared from degradable polymers such as poly(lactide-co-glycolide) copolymers. One limitation of using preformed microspheres for embolization is that they cannot be delivered to small vessels.
Rhee et al. (U.S. Pat. No. 5,752,974) describe an injectable or implantable biomaterial for filling or blocking lumens or voids of the body. The injectable or implantable biomaterial is formed by reacting a polymer with a hydrophilic crosslinking agent.
Tissues adhesives formed by reacting an oxidized polysaccharide with a water-dispersible, multi-arm polyether amine have been reported (Kodokian et al., copending and commonly owned U.S. Patent Application Publication No. 2006/0078536); however, the use of the materials for embolization treatment is not described.
Therefore, the problem to be solved is to provide a degradable embolic material that can be delivered to small vessels. The stated problem is addressed herein by the discovery that a hydrogel formed by the in situ reaction of an oxidized polysaccharide with a water dispersible, multi-arm amine may act as an effective degradable embolic material.